Detection of parent-of-origin effects based on complete and incomplete nuclear families with multiple affected children.
Parent-of-origin effects are important in studying genetic traits. More than 1% of all mammalian genes are believed to show parent-of-origin effects. Some statistical methods may be ineffective or fail to detect linkage or association for a gene with parent-of-origin effects. Based on case-parents trios, the parental-asymmetry test (PAT) is simple and powerful in detecting parent-of-origin effects. However, it is common in practice to collect nuclear families with both parents as well as nuclear families with only one parent. In this paper, when only one parent is available for each family with an arbitrary number of affected children, we firstly develop a new test statistic 1-PAT to test for parent-of-origin effects in the presence of association between an allele at the marker locus under study and a disease gene. Then we extend the PAT to accommodate complete nuclear families each with one or more affected children. Combining families with both parents and families with only one parent, the C-PAT is proposed to detect parent-of-origin effects. The validity of the test statistics is verified by simulation in various scenarios of parameter values. A power study shows that using the additional information from incomplete nuclear families in the analysis greatly improves the power of the tests, compared to that based on only complete nuclear families. Also, utilizing all affected children in each family, the proposed tests have a higher power than when only one affected child from each family is selected. Additional power comparison also demonstrates that the C-PAT is more powerful than a number of other tests for detecting parent-of-origin effects.
Zhou
Ji-Yuan
JY
Department of Statistics and Actuarial Science, University of Hong Kong, Hong Kong, China.
Hu
Yue-Qing
YQ
Lin
Shili
S
Fung
Wing K
WK
D002648:Child; D003198:Computer Simulation; D018392:Genomic Imprinting; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D009679:Nuclear Family; D010290:Parents